The limits of stimulation of the immunomodulatory
alkaloid swainsonine (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) were studied in inbred C57BL/6 mice for potential support of intense high dose
cancer chemotherapy and/or radiation because of its attractive pharmacologic profile on the hematopoietic system. Specifically, the effects of
swainsonine on bone marrow cellularity and on in vitro progenitor cell proliferation to total colony forming units (CFU) and differentiation to different lineages were studied as a function of number of days post
drug administration. The lineages evaluated were colony forming units-granulocyte-macrophage (CFU-GM), erythroid-burst forming units (BFU-e) and CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM or CFU-Mix). Groups of mice were treated with
swainsonine or plain vehicle,
phosphate buffered saline for 10 consecutive days. The effects of these agents on the hematopoietic system were studied up to 60 days following their discontinuation. The magnitude of the effects of
swainsonine on bone marrow system gradually declined with increasing duration of days following its discontinuation. Nevertheless, its residual stimulatory effects on bone marrow cellularity, total CFU, CFU-GM, BFU-e and CFU-Mix continued to be significant (P<0.0001) up to 45, 50, 50, 55 and 50 days, respectively, compared to those of diluent
buffer or untreated controls. Since
cancer chemotherapeutic agents or radiation are normally given in schedules and/or cycles, these results strongly suggest that
swainsonine effects are sustained long enough to potentially support and facilitate hematopoietic recovery during anti-
cancer cytotoxic treatment.